肝细胞癌（HCC）是一种患病率和死亡率较高的恶性肿瘤，但迄今为止缺乏有效治疗方法。尽管近年来免疫检查点抑制剂的出现为HCC的治疗带来了希望，但仍有相当数量的患者无法获得持久和理想的临床效益。因此，改进免疫检查点抑制剂的组合以增强治疗效果已成为全球研究的热点。几种组蛋白去乙酰化酶2（HDAC2）抑制剂在许多实体瘤中已显示出优势，但在HCC中尚未被应用。此外，最新的证据表明，HDAC2抑制剂可以调控PD-L1的乙酰化，从而阻断PD-L1的核转位，进而增强PD-1/PD-L1抑制剂的疗效，提高抗癌免疫力。此外，我们团队最近发现了一种新型HDAC2抑制剂（HDAC2i），瓦利酸（VA），作为单药疗法在HCC治疗中具有巨大潜力。因此，将HDAC2抑制剂与免疫检查点抑制剂结合的新型组合策略已经出现，并具有重要的发展价值。本文旨在激发对理想HDAC2抑制剂应用于HCC免疫治疗中具有实体抗肿瘤效应的探索的热情。 © 2023. BioMed Central Ltd., part of Springer Nature.

Hepatocellular carcinoma (HCC) is a malignancy with high morbidity and mortality but lacks effective treatments thus far. Although the emergence of immune checkpoint inhibitors in recent years has shed light on the treatment of HCC, a considerable number of patients are still unable to achieve durable and ideal clinical benefits. Therefore, refining the combination of immune checkpoint inhibitors (ICIs) to enhance the therapeutic effect has become a global research hotspot. Several histone deacetylase 2 inhibitors have shown advantages in ICIs in many solid cancers, except for HCC. Additionally, the latest evidence has shown that histone deacetylase 2 inhibition can regulate PD-L1 acetylation, thereby blocking the nuclear translocation of PD-L1 and consequently enhancing the efficacy of PD-1/PD-L1 inhibitors and improving anti-cancer immunity. Moreover, our team has recently discovered a novel HDAC2 inhibitor (HDAC2i), valetric acid (VA), that possesses great potential in HCC treatment as a monotherapy. Thus, a new combination strategy, combining HDAC2 inhibitors with ICIs, has emerged with significant development value. This perspective aims to ignite enthusiasm for exploring the application of ideal HDAC2 inhibitors with solid anti-tumor efficacy in combination with immunotherapy for HCC.© 2023. BioMed Central Ltd., part of Springer Nature.